This proposal requests support (1) to add drug ejection techniques to the methods by which we examine the function of the cerebral neocortex and (2) to carry out preliminary studies with this methodology that begin to examine the functional role of cortical cholinergic input. We will combine drug ejection with neural recording to test the hypothesis that the widespread cholinergic input to cortex modulates the effectiveness of sensory inputs. First, we will confirm previous studies that have demonstrated a selective effect of acetylcholine on specific subsets of cortical neurons, and next we will identify changes in the response of neurons in the somatic sensorimotor cortex to peripheral stimulation when cholinergic agonists or antagonists are applied. The results will provide evidence relating to the ability of the cholinergic system to modify the way cortical neurons respond to specific sensory inputs and will be the basis for a major grant designed to examine the role of cortical cholinergic systems in memory, learning, and in memory disorders such as Alzheimer's disease.